OMIA:002757-9615 : Ataxia, cerebellar, RALGAPA1-related in Canis lupus familiaris (dog)
Categories: Nervous system phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2023
Molecular basis: Christen et al. (2023) identified a likely causal variant in Belgian shepherd dogs: "Combined linkage and homozygosity mapping delineated a 5.5 Mb critical interval. The comparison of whole-genome sequence data of one affected dog to 929 control genomes revealed a private homozygous ~4.8 kb deletion in the critical interval, Chr8:14,468,376_14,473,136del4761. The deletion comprises exon 35 of the RALGAPA1 gene, XM_038544497.1:c.6080-2893_6944+1003del. It is predicted to introduce a premature stop codon into the transcript, truncating ~23% of the wild-type open reading frame of the encoded Ral GTPase-activating protein catalytic subunit α 1, XP_038400425.1:(p.Val2027Glnfs*7)."
Clinical features: Christen et al. (2023) "investigated a [Belgian shepherd] litter in which two puppies developed cerebellar ataxia. The clinical signs stabilized at around six weeks of age, but remained visible into adulthood. ... Genotyping additional ataxic Belgian shepherd dogs revealed three additional homozygous mutant dogs from a single litter, which had been euthanized at five weeks of age due to their severe clinical phenotype."
Pathology: Christen et al. (2023): "Histopathology revealed cytoplasmic accumulation of granular material within cerebellar Purkinje cells [in affected Belgian shepherds]."
Prevalence: Christen et al. (2023): "Genotyping a cohort of almost 900 Belgian shepherd dogs [for the ~4.8 kb deletion] showed ... a carrier frequency of 5% in the population."
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|RALGAPA1||Ral GTPase activating protein, alpha subunit 1 (catalytic)||Canis lupus familiaris||8||NC_051812.1 (14570610..14327816)||RALGAPA1||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1613||Belgian Shepherd||Ataxia, cerebellar, RALGAPA1-related||RALGAPA1||deletion, gross (>20)||Naturally occurring variant||UU_Cfam_GSD_1.0||8||g.14468376_14473136del||c.6080-2893_6944+1003del||p.(V2027Qfs*7)||XM_038544497.1; XP_038400425.1; published as g.14,468,376_14,473,136del4761||2023||37628572|
Cite this entry
|2023||Christen, M., Zdora, I., Leschnik, M., Jagannathan, V., Puff, C., Hünerfauth, E., Volk, H.A., Baumgärtner, W., Koch, T.C., Schäfer, W., Kleiter, M., Leeb, T. :|
|RALGAPA1 deletion in Belgian shepherd dogs with cerebellar ataxia. Genes (Basel) 14:, 2023. Pubmed reference: 37628572 . DOI: 10.3390/genes14081520.|
- Created by Imke Tammen2 on 27 Aug 2023
- Changed by Tosso Leeb on 30 Aug 2023